Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine.

TLDR

IL‑7 is a potent growth factor for immature T and B cells and, to a lesser extent, for mature T cells. The study aimed to inactivate the IL‑7 gene in mice to clarify its role in lymphocyte development. Using gene‑targeting techniques, the IL‑7 gene was knocked out in the mouse germline. IL‑7‑deficient mice exhibit profound lymphopenia, with blocked B‑cell maturation at the pro‑B to pre‑B stage, a 20‑fold drop in thymic cellularity while preserving CD4/CD8 ratios, a 10‑fold reduction in splenic T cells, and an abnormal accumulation of immature B cells, yet remaining lymphocytes respond normally to mitogens, demonstrating that IL‑7 is indispensable for T and B cell development and representing the first single‑cytokine knockout with severe lymphoid defects.

Abstract

Interleukin (IL)-7 is a potent stimulus for immature T and B cells and, to a lesser extent, mature T cells. We have inactivated the IL-7 gene in the mouse germline by using gene-targeting techniques to further understand the biology of IL-7. Mutant mice were highly lymphopenic in the peripheral blood and lymphoid organs. Bone marrow B lymphopoiesis was blocked at the transition from pro-B to pre-B cells. Thymic cellularity was reduced 20-fold, but retained normal distribution of CD4 and CD8. Splenic T cellularity was reduced 10-fold. Splenic B cells, also reduced in number, showed an abnormal population of immature B cells in adult animals. The remaining splenic populations of lymphocytes showed normal responsiveness to mitogenic stimuli. These data show that proper T and B cell development is dependent on IL-7. The IL-7-deficient mice are the first example of single cytokine-deficient mice that exhibit severe lymphoid abnormalities.